Influencing Factors of Urinary Iodine Concentration Before and After Radioiodine Therapy for Differentiated Thyroid Cancer: An Initial Exploration of the Relationship With Therapeutic Efficacy.

OBJECTIVE: To investigate the impact of urinary iodine concentration (UIC) and post-stimulatory thyroglobulin (ps-Tg) levels on the therapeutic efficacy of differentiated thyroid cancer (DTC) patients after initial radioiodine therapy, and to analyze the validity of these indicators as prognostic factors. METHODS: A total of 213 DTC patients received initial radioiodine therapy from June 2022 to September 2023. Demographic data and UIC were collected before and after therapy. Thyrotropin, thyroglobulin (Tg), and thyroglobulin antibody levels were assessed. Iodine uptake rate was measured, and therapeutic efficacy was evaluated 6 months post-therapy. Statistical tests were used for data comparison, and logistic regression analysis for response factors. RESULTS: Post-therapy UIC and pre-post UIC difference were significantly correlated with Tg levels but not with reaching excellent response (ER) indicated by suppression of Tg levels below 0.2 ug/L. Ps-Tg levels related to therapeutic efficacy, while UIC did not correlate with outcomes. ROC curve analysis found optimal ps-Tg cut-off points for the low-intermediate and high-risk groups classified by primary tumor size, invasion, metastasis, and pathological type. CONCLUSION: Post-treatment UIC and pre-post UIC difference correlate with ps-Tg levels. Ps-Tg levels are an associated factor for DTC, but UIC changes, despite correlation with ps-Tg, are not significantly related to outcomes and cannot be used as a prognostic factor.

ObjectiveTo investigate the impact of urinary iodine concentration (UIC) and post-stimulatory thyroglobulin (ps-Tg) levels on the therapeutic efficacy of differentiated thyroid cancer (DTC) patients after initial radioiodine therapy, and to analyze the validity of these indicators as prognostic factors.Methods213 DTC patients received initial radioiodine therapy from June 2022 to September 2023. Demographic data and UIC were collected before and after therapy. Thyrotropin, thyroglobulin, and thyroglobulin antibody levels were assessed. Iodine uptake rate was measured, and therapeutic efficacy evaluated 6 months post-therapy. Statistical tests were used for data comparison and logistic regression analysis for response factors.ResultsPost-therapy UIC and pre-post UIC difference were significantly correlated with thyroglobulin levels but not with reaching excellent response (ER) where suppression of Tg levels below 0.2ug/l. Ps-Tg levels related to therapeutic efficacy, while UIC did not correlate with outcomes. ROC curve analysis found optimal ps-Tg cut-off points for low-intermediate and high-risk groupsclassified by primary tumor size, invasion, metastasis, and pathological type.ConclusionPost-treatment UIC and pre-post UIC difference correlate with ps-Tg levels. Ps-Tg levels are an associated factor for DTC, but UIC changes, despite correlation with ps-Tg, are not significantly related to outcomes and cannot be used as a prognostic factor.

Comparative efficiency of differential diagnostic methods for the identification of BRAF V600E gene mutation in papillary thyroid cancer (Review).

V-Raf murine sarcoma viral oncogene homolog B1 (BRAF) encodes a serine-threonine kinase. The V600E point mutation in the BRAF gene is the most common mutation, predominantly occurring in melanoma, and colorectal, thyroid and non-small cell lung cancer. Particularly in the context of thyroid cancer research, it is routinely employed as a molecular biomarker to assist in diagnosing and predicting the prognosis of papillary thyroid cancer (PTC), and to formulate targeted therapeutic strategies. Currently, several methods are utilized in clinical settings to detect BRAF V600E mutations in patients with PTC. However, the sensitivity and specificity of various detection techniques vary significantly, resulting in diverse detection outcomes. The present review highlights the advantages and disadvantages of the methods currently employed in medical practice, with the aim of guiding clinicians and researchers in selecting the most suitable detection approach for its high sensitivity, reproducibility and potential to develop targeted therapeutic regimens for patients with BRAF gene mutation-associated PTC.

Effect evaluation of different preventive measures for ileus after abdominal operation: A systematic review and network meta-analysis.

Background: Different approaches to the prevention of postoperative ileus have been evaluated in numerous randomized controlled trials. This network meta-analysis aimed to investigate the relative effectiveness of different interventions in preventing postoperative ileus. Methods: Randomized controlled trials (RCTS) on the prevention of postoperative ileus were screened from Chinese and foreign medical databases and compared. STATA software was used for network meta-analysis using the frequency method. Random-effects network meta-analysis was also used to compare all schemes directly and indirectly. Results: A total of 105 randomized controlled trials with 18,840 participants were included in this report. The results of the network meta-analysis showed that intravenous analgesia was most effective in preventing the incidence of postoperative ileus, the surface under the cumulative ranking curve (SUCRA) is 90.5. The most effective intervention for reducing the first postoperative exhaust time was postoperative abdominal mechanical massage (SUCRA: 97.3), and the most effective intervention for reducing the first postoperative defecation time was high-dose opioid antagonists (SUCRA: 84.3). Additionally, the most effective intervention for reducing the time to initiate a normal diet after surgery was accelerated rehabilitation (SUCRA: 85.4). A comprehensive analysis demonstrated the effectiveness and prominence of oral opioid antagonists and electroacupuncture (EA) combined with gum. Conclusion: This network meta-analysis determined that oral opioid antagonists and EA combined with chewing gum are the most effective treatments and optimal interventions for reducing the incidence of postoperative ileus. However, methods such as abdominal mechanical massage and coffee require further high-quality research.

Selective internal radiation therapy with yttrium-90 resin microspheres followed by anatomical hepatectomy: A potential curative strategy in advanced hepatocellular carcinoma.

About 80% of hepatocellular carcinoma (HCC) patients are in advanced stages and ineligible for curative surgery. Palliative treatments just maintained limited survival, thus an effective downstaging therapy is badly needed. Here we report an initially unresectable patient who underwent radical hepatectomy after successful downstaging with selective internal radiation therapy (SIRT). A 34-year-old man was diagnosed with China Liver Cancer Staging (CNLC) IIIa HCC. Due to insufficient future liver remnant and vascular involvement, the patient was suggested to be unresectable. SIRT with yttrium-90 resin microspheres was given. At three months post-SIRT, a complete response was achieved. The tumor was downstaged to CNLC Ia stage. The patient underwent anatomical hepatectomy 5 months after SIRT. Histopathological examination of the resected specimen showed 4% viable tumor cells inside a necrotic mass. To our knowledge, this is the first case who underwent SIRT with yttrium-90 resin microspheres in China mainland. The success of the downstaging in this case renders a possible cure to be achieved in an initially unresectable patient. In addition, the nearly complete tumor necrosis in the resected specimen indicates a good prognosis post-surgery. This is the first case who underwent SIRT with yttrium-90 resin microspheres in China mainland. SIRT followed by anatomical hepatectomy is a potentially curative strategy for unresectable HCC, which deserves a confirmative trial in the future.

Deep learning nomogram for preoperative distinction between Xanthogranulomatous cholecystitis and gallbladder carcinoma: A novel approach for surgical decision.

The distinction between Xanthogranulomatous Cholecystitis (XGC) and Gallbladder Carcinoma (GBC) is challenging due to their similar imaging features. This study aimed to differentiate between XGC and GBC using a deep learning nomogram model built from contrast enhanced computed tomography (CT) scans. 297 patients were included with confirmed XGC (94) and GBC (203) as the training and internal validation cohort from 2017 to 2021. The deep learning model Resnet-18 with Fourier transformation named FCovResnet18, shows most impressive potential in distinguishing XGC from GBC using 3-phase merged images. The accuracy, precision and area under the curve (AUC) of the model were then calculated. An additional cohort of 74 patients consisting of 22 XGC and 52 GBC patients was enrolled from two subsidiary hospitals as the external validation cohort. The accuracy, precision and AUC achieve 0.98, 0.99, 1.00 in the internal validation cohort and 0.89, 0.92, 0.92 in external validation cohort. A nomogram model combining clinical characteristics and deep learning prediction score showed improved predicting value. Altogether, FCovResnet18 nomogram has demonstrated its ability to effectively differentiate XGC from GBC preoperatively, which significantly aid surgeons in making informed and accurate surgical decisions for XGC and GBC patients.

Therapeutic effect of vitamin D in Hashimoto's thyroiditis: a prospective, randomized and controlled clinical trial in China.

BACKGROUND: The study aims to explore the clinical effects of Vitamin D (VitD) supplements for Hashimoto's Thyroiditis (HT), which are unclear according to other studies. METHODS: Female patients with newly diagnosed HT from January to June in 2018 were included. This study is registered in the Chinese Clinical Trials Registry with registration number ChiCTR1800014619 (URL: https://www.chictr.org.cn/). Patients were randomly assigned to the treatment group and the control group. The treated group were further randomly assigned to a VitD supplement group or VitD & Levothyroxine (L-T4) supplement group. After 6 months, we recorded and compared various indicators between different groups. RESULTS: A total of 179 patients, aged 12 to 75, were used for statistical analysis. A significant decrease in Thyroid Peroxidase Antibody (TPOAb) level was observed (351.70±183.25 vs. 246.37±157.39, P<0.001) in the VitD-treated group compared to the control group after 6 months. Free Triiodothyronine (FT3) and Free Thyroxine (FT4) level were increased (FT3: 4.30±0.64 vs. 4.84±0.9, P<0.001; FT4: 15.15±1.93 vs. 17.38±2.97, P<0.001), and Thyroid-Stimulating Hormone (THS) level was decreased (3.58±1.78 vs. 2.25±1.22, P<0.001) in the VitD-treated group compared to the control group. CONCLUSION: VitD supplementation can effectively slow progression of hypothyroidism, improve thyroid function, and reduce the anti-thyroid antibody level. This suggests it is useful for HT.

Construction of an immune-related lncRNA-miRNA-mRNA regulatory network in radiation-induced esophageal injury in rats.

Radiation-induced esophageal injury (RIEI) is an adverse reaction of radiation therapy in patients with esophageal cancer, lung cancer and other malignant tumors. Competitive endogenous RNA (ceRNA) network is known to play a significant role in the onset and progression of many diseases, but the exact mechanism of ceRNA in RIEI has not been fully elucidated. In this study, rat esophaguses were obtained after conducting irradiation under different doses (0 Gy, 25 Gy, 35 Gy). Total RNA was extracted and mRNA, lncRNA, circRNA, and miRNA sequencing was performed. Multiple dose-dependent differentially expressed RNAs (dd-DERs), including 870 lncRNAs, 82 miRNAs, 2478 mRNAs, were obtained through the integration of differential expression analysis and dose-dependent screening (35 Gy ≥ 25 Gy > 0 Gy, or 35 Gy ≤ 25 Gy < 0 Gy). Co-expression analysis and prediction of the binding site in dd-DER were conducted and 27 lncRNAs, 20 miRNAs, and 168 mRNAs were selected to construct a ceRNA network. As the immune microenvironment is crucial for RIEI progression, we constructed an immune-related ceRNA network consisting of 11 lncRNAs, 9 miRNAs, and 9 mRNAs. The expression levels of these immune-related RNAs were verified by RT-qPCR. Immune infiltration analysis showed that the RNAs in the immune-related ceRNA network were mainly associated with the proportion of monocytes, M2 macrophages, activated NK cells, and activated CD4+ memory T cells. Drug sensitivity analysis was conducted based on the expression levels of mRNAs in the immune-related ceRNA network, and small molecule drugs with preventive and therapeutic effects on RIEI were identified. In summary, an immune-related ceRNA network associated with RIEI progression was constructed in this study. The findings provide useful information on new potential targets for the prevention and treatment of RIEI.

Molecular response of keloids to ionizing radiation: targeting FOXO1 radiosensitizes keloids.

PURPOSE: Keloids are benign dermal tumors that arise from abnormal wound healing processes following skin lesions. Surgical excision followed by radiotherapy plays an important role in the treatment of keloids. Nevertheless, radioresistance remains a serious impediment to treatment efficacy. Investigation of the molecular response of keloids to radiation may contribute to radiosensitizing strategies. MATERIALS AND METHODS: Primary keloid fibroblasts from human keloids were isolated and irradiated with X-ray. The expression profiles of messenger RNA (mRNA) in nonradiated and irradiated primary keloid fibroblasts were measured by mRNA sequencing analysis. Then, we identified common motifs and corresponding transcription factors of dysregulated mRNAs by using bioinformatic analysis of the proximal promoters. Whereafter, GO and KEGG were used to analyze the functional enrichment of the differentially expressed genes. RESULTS: We found that radiation not only suppressed proliferation but also increased cell senescence of primary keloid fibroblasts. There were 184 mRNAs and 204 mRNAs that showed significant changes in 4 and 8 Gy irradiated primary keloid fibroblasts, respectively. Among them, 8 upregulated and 30 downregulated mRNAs showed consistent alterations in 4 and 8 Gy irradiated primary keloid fibroblasts. More importantly, the xForkhead box O1 (FOXO1) signaling pathway was involved in the irradiation response. Pretreatment with the FOXO1 signaling inhibitor AS1842856 significantly promoted LDH release, apoptosis and senescence of primary keloid fibroblasts following irradiation. CONCLUSION: Our findings illustrated the molecular changes in human keloid fibroblasts in response to radiation, and FOXO1 pathway inhibition is expected to provide a novel strategy for the radiosensitization of keloids.

The role of human antigen R (HuR) in modulating proliferation, senescence and radiosensitivity of skin cells.

The skin is the largest outermost organ of the human body. It is vulnerable to various damages, such as ionizing radiation. Exploration of proliferation, senescence and radiosensitivity of skin cells contributes to the development of medical and cosmetic countermeasures against skin aging and toward injury protection. Human antigen R (HuR) is one of the most widely studied RNA-binding proteins and serves an important role in stabilization of mRNA and regulation of the expression of the target genes. To investigate the role of HuR in modulating proliferation, senescence and radiosensitivity of skin cells, the present study performed an in vitro study using lentivirus-mediated overexpression or silencing of HuR in human keratinocyte HaCaT cells and human skin fibroblast WS1 cells. The results indicated that overexpression of HuR promoted proliferation, whereas downregulation of HuR inhibited proliferation of HaCaT and WS1 cells. Overexpression of HuR reduced apoptosis and senescence in skin cells. RNA-Seq of skin cells with HuR overexpression or knockdown identified 77 mRNAs positively or negatively correlated with HuR expression levels. In addition, silencing of HuR induced a significant increase in radiogenic reactive oxygen species after irradiation. Overexpression of HuR increased radiotolerance of HaCaT and WS1 cells. RNA immunoprecipitation coupled with RNA-Seq identified 14 mRNAs interacting with HuR upon radiation exposure. Overall, the findings of the present study illustrated the key role of HuR in modulating proliferation, senescence and radiosensitivity of skin cells providing a new therapeutic strategy for cosmetic treatments and to combat skin injury.

Drainage volume on postoperative day one to predict clinically relevant postoperative pancreatic fistula following distal pancreatectomy.

BACKGROUND: The purpose of this study was to determine how the drain fluid volume on the first day after surgery (DFV 1) can be used to predict clinically relevant post-operative pancreatic fistula following distal pancreatectomy (DP). METHOD: A retrospective analysis of 175 patients who underwent distal pancreatectomy in hepatobiliary surgery at Chengdu 363 Hospital (China) from January 2015 to January 2021 has been performed. Depending on the presence of pancreatic fistula, all patients were divided into two groups: POPF and non-POPF. The clinical factors were analyzed using SPSS 17.0 and Medcalc software. In order to assess the effectiveness of DFV 1 in predicting POPF after surgery, ROC curves were used to calculate its cut-off point,, which yielded sensitivity and negative predictive value of 100% for excluding POPF. RESULT: Of the 175 patients who underwent distal pancreatectomy, the incidence of overall pancreatic fistula was 36%, but the rate of clinically significant (grade B and C) fistula, as defined by the International Study Group on Pancreatic Fistula, 30 was only 17.1% (28 grade B and 2 grade C fistula). The results from univariate and multivariate logistic regression analysis showed that drain fluid volume on the first postoperative day (OR = 0.95, P = 0.03), drainage fluid amylase level on POD1 (OR = 0.99, P = 0.01) and the preoperative ALT level (OR = 0.73, P = 0.02) were independent risk factors associated with CR-POPF. Receiver operating characteristic (ROC) curve analysis revealed that a drainage volume of 156 mL within 24 h and an amylase greater than 3219.2 U/L on the first postoperative day were the optimal thresholds associated with complications. CONCLUSION: After distal pancreatectomy, the drainage volume on the first postoperative day can predict the presence of a clinically relevant pancreatic fistula.

Proteomic and miRNA profiling of radon-induced skin damage in mice: FASN regulated by miRNAs.

Radon is a naturally occurring radioactive gas and considered as a serious carcinogen to humans. Continuous radioactive decay of this gas emits high-energy alpha particles. Long-term radon exposure induces oxidative stress and inflammatory response, which results in chronic lung diseases. However, biological effects after radon exposure in other organs have been rarely reported. As the outermost organ of the human body, the skin suffers from environmental damage to agents such as air pollution. Epidemiological studies indicated that areas with high level of radon had a high incidence of skin cancer. However, whether radon exposure induces skin damage has not been reported yet. In this study, we established a radon-exposed mouse model and found that radon exposure affected the structure of skin tissues, which was manifested by inflammatory cell infiltration and skin atrophy. Using proteomic approach, we found 45 preferentially expressed proteins in 60 Working Level Months (WLM) group and 314 preferentially expressed proteins in 120 WLM group from radon-exposed skin tissues. Through microRNA (miRNA) sequencing profiling analysis, 57 dysregulated miRNAs were screened between the control and radon-treated mouse skin. By integrating the dysregulated proteins and miRNAs, radon-induced fatty acid synthase (FASN) was investigated in greater detail. Results showed that FASN was regulated by miR-206-3p and miR-378a-3p and involved in the pathogenesis of radon-induced skin damage. Overexpression of FASN inhibited the proliferation, and induced in WS1 cells. Our present findings illustrate the molecular change during radon-induced skin damage and the potential role of FASN during this process.

Long-Term Prognostic Factors in Patients With Antineutrophil Cytoplasmic Antibody-Associated Vasculitis: A 15-Year Multicenter Retrospective Study.

Background: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a multisystem autoimmune disease with small-vessel involvement. In AAV, microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA) are major clinicopathologic variants. In addition, myeloperoxidase (MPO) and proteinase 3 (PR3) are major target antigens. The objective of the study was to explore the predictive factors for long-term survival in AAV patients. Materials and Methods: A multicenter retrospective study was carried out on 407 patients between 2005 and 2020. Clinical parameters were obtained from laboratory tests including the ANCA types, antinuclear antibody (ANA), extractable nuclear antigen (ENA), anti-streptolysin O (ASO), glomerular filtration rate (GFR), and the laboratory examinations for the blood routine, liver function, renal function, and immunity, etc. The data for clinical parameters were collected from electronic medical records (EMRs), and the data for patient survival were acquired through regular follow-up. The association of clinical parameters with overall survival (OS) along with 3-year and 5-year survival rates was analyzed, and the nomogram as a predictive model was established according to the analysis results. Results: In the present study, 336 (82.6%) patients and 46 (11.3%) patients were diagnosed with MPA and GPA, respectively. The mean and median OS for all the patients were 2,285 and 2,290 days, respectively. The 1-year, 3-year, 5-year, and 10-year cumulative survival rates for all the patients were 84.2%, 76.3%, 57.2%, and 32.4%, respectively. Univariate and multivariate survival analyses indicated that the independent prognostic factors included age, pathological categories (MPA, GPA, and other types), serum ANCA types (negative or positive for MPO and/or PR3), ANA, ASO, GFR, lymphocyte, neutrophil-to-lymphocyte ratio (NLR), and C-reactive protein (CRP), and these clinical parameters except for ASO were used to construct a nomogram. The nomogram for 3-year and 5-year survival rates had a C-index of 0.721 (95% CI 0.676-0.766). The calibration curves showed that the predicted values of the nomogram for 3-year and 5-year survival rates were generally consistent with practical observed values, and decision curve analysis (DCA) further demonstrated the practicability and accuracy of the predictive model. Conclusion: Laboratory tests at diagnosis have great significance in the prediction of long-term survival in AAV patients.

Construction of a Tumor Immune Microenvironment-Related Prognostic Model in BRAF-Mutated Papillary Thyroid Cancer.

BRAF mutation is a representative oncogenic mutation, with a frequency of 60% in papillary thyroid carcinoma (PTC), but the reasons for the poor prognosis and more aggressive course of BRAF-mutated PTC are controversial. Tumor immune microenvironment (TIME) is an essential factor permitting the development and progression of malignancy, but whether TIME participates in the prognosis of BRAF-mutated PTC has not yet been reported. The primary goal of the present study was to provide a comprehensive TIME-related prognostic model to increase the predictive accuracy of progression-free survival (PFS) in patients with BRAF-mutated PTC. In this study, we analyzed the mRNA-seq data and corresponding clinical data of PTC patients obtained from the TCGA database. By calculating the TIME scores (immune score, stromal score and ESTIMATE score), the BRAF mutation group (n=237) was dichotomized into the high- and low-score groups. By functional analysis of differentially expressed genes (DEGs) in different high/low score groups, we identified 2 key TIME-related genes, HTR3A and NIPAL4, which affected PFS in BRAF-mutated PTC. A risk scoring system was developed by multivariate Cox analysis based on the abovementioned 2 TIME-related genes. Then, the BRAF-mutated cohort was divided into the high- and low-risk groups using the median risk score as a cutoff. A high risk score correlated positively with a higher HTR3A/NIPAL4 expression level but negatively with PFS in BRAF-mutated PTC. Ultimately, a nomogram was constructed by combining risk score with clinical parameter (Tumor stage), and the areas under the ROC curve (AUCs) of the nomogram for predicting 1-, 3- and 5-year PFS were then calculated and found to be 0.694, 0.707 and 0.738, respectively, indicating the improved accuracy and clinical utility of the nomogram versus the risk score model in the BRAF-mutated PTC cohort. Moreover, we determined the associations between prognostic genes or risk score and immune cell infiltration by two-way ANOVA. In the high-risk score, high HTR3A expression, and high NIPAL4 expression groups, higher infiltration of immune cells was found. Collectively, these findings confirm that the nomogram is effective in predicting the outcome of BRAF-mutated PTC and will add a spatial dimension to the developing risk stratification system.

Transcriptome Profiling Unveils a Critical Role of IL-17 Signaling-Mediated Inflammation in Radiation-Induced Esophageal Injury in Rats.

Elucidation of the molecular mechanisms involving the initiation and progression of radiation-induced esophageal injury (RIEI) is important for prevention and treatment. Despite ongoing advances, the underlying mechanisms controlling RIEI remain largely unknown. In the present study, RNA-seq was performed to characterize mRNA profiles of the irradiated rat esophagus exposed to 0, 25, or 35 Gy irradiation. Bioinformatics analyses including dose-dependent differentially expressed genes (DEGs), Gene Ontology (GO), Kyoto Encyclopedia of Gene and Genome (KEGG) pathway, protein-protein interaction (PPI) network, and immune infiltration were performed. 134 DEGs were screened out with a dose-dependent manner (35 Gy > 25 Gy > control, or 35 Gy < 25 Gy < control). GO and KEGG analyses showed that the most significant mechanism was IL-17 signaling-mediated inflammatory response. 5 hub genes, Ccl11, Cxcl3, Il17a, S100a8, and S100a9, were identified through the intersection of the DEGs involved in inflammatory response, IL-17 pathway, and PPI network. Additionally, immune infiltration analysis showed the activation of macrophages, monocytes, T cells, NKT cells, and neutrophils, among which macrophages, monocytes, and neutrophils might be the main sources of S100a8 and S100a9. Thus, these findings further our understanding on the molecular biology of RIEI and may help develop more effective therapeutic strategies.

Construction of a Signature Model to Predict the Radioactive Iodine Response of Papillary Thyroid Cancer.

Papillary thyroid cancer (PTC) accounts for about 90% of thyroid cancer. There are approximately 20%-30% of PTC patients showing disease persistence/recurrence and resistance to radioactive iodine (RAI) treatment. For these PTC patients with RAI refractoriness, the prognosis is poor. In this study, we aimed to establish a comprehensive prognostic model covering multiple signatures to increase the predictive accuracy for progression-free survival (PFS) of PTC patients with RAI treatment. The expression profiles of mRNAs and miRNAs as well as the clinical information of PTC patients were extracted from TCGA and GEO databases. A series of bioinformatics methods were successfully applied to filtrate a two-RNA model (IPCEF1 and hsa-mir-486-5p) associated with the prognosis of RAI-therapy. Finally, the RNA-based risk score was calculated based on the Cox coefficient of the individual RNA, which achieved good performances by the time-dependent receiver operating characteristic (tROC) curve and PFS analyses. Furthermore, the predictive power of the nomogram, integrated with the risk score and clinical parameters (age at diagnosis and tumor stage), was assessed by tROC curves. Collectively, our study demonstrated high precision in predicting the RAI response of PTC patients.

Phase-shift nanodroplets as an emerging sonoresponsive nanomaterial for imaging and drug delivery applications.

Nanodroplets - emerging phase-changing sonoresponsive materials - have attracted substantial attention in biomedical applications for both tumour imaging and therapeutic purposes due to their unique response to ultrasound. As ultrasound is applied at different frequencies and powers, nanodroplets have been shown to cavitate by the process of acoustic droplet vapourisation (ADV), causing the development of mechanical forces which promote sonoporation through cellular membranes. This allows drugs to be delivered efficiently into deeper tissues where tumours are located. Recent reviews on nanodroplets are mostly focused on the mechanism of cavitation and their applications in biomedical fields. However, the chemistry of the nanodroplet components has not been discussed or reviewed yet. In this review, the commonly used materials and preparation methods of nanodroplets are summarised. More importantly, this review provides examples of variable chemistry components in nanodroplets which link them to their efficiency as ultrasound-multimodal imaging agents to image and monitor drug delivery. Finally, the drawbacks of current research, future development, and future direction of nanodroplets are discussed.

Metabolic Profiling Implicates a Critical Role of Cyclooxygenase-2-Mediated Arachidonic Acid Metabolism in Radiation-Induced Esophageal Injury in Rats.

Radiation-induced esophageal injury (RIEI) is a major dose-limiting complication of radiotherapy, especially for esophageal and thoracic cancers. RIEI is a multi-factorial and multi-step process, which is regulated by a complex network of DNA, RNA, protein and metabolite. However, it is unclear which esophageal metabolites are altered by ionizing radiation and how these changes affect RIEI progression. In this work, we established a rat model of RIEI with 0-40 Gy X-ray irradiation. Esophageal irradiation using ≥25 Gy induced significant changes to rats, such as body weight, food intake, water intake and esophageal structure. The metabolic changes and related pathways of rat esophageal metabolites were investigated by liquid chromatography-mass spectrometry (LC-MS). One hundred eighty metabolites showed an up-regulation in a dose-dependent manner (35 Gy ≥ 25 Gy > controls), and 199 metabolites were downregulated with increasing radiation dose (35 Gy ≤ 25 Gy < controls). The KEGG analysis showed that ionizing radiation seriously disrupted multiple metabolic pathways, and arachidonic acid metabolism was the most significantly enriched pathway. 20 metabolites were dysregulated in arachidonic acid metabolism, including up-regulation of five prostaglandins (PGA2, PGJ2, PGD2, PGH2, and PGI2) in 25 or 35 Gy groups. Cyclooxygenase-2 (COX-2), the key enzyme in catalyzing the biosynthesis of prostaglandins from arachidonic acid, was highly expressed in the esophagus of irradiated rats. Additionally, receiver operating characteristic (ROC) curve analysis revealed that PGJ2 may serve as a promising tissue biomarker for RIEI diagnosis. Taken together, these findings indicate that ionizing radiation induces esophageal metabolic alterations, which advance our understanding of the pathophysiology of RIEI from the perspective of metabolism.

Role of AUF1 in modulating the proliferation, migration and senescence of skin cells.

AU-rich element RNA-binding factor 1 (AUF1) is a classical RNA-binding protein. AUF1 influences the process of development, apoptosis and tumorigenesis by interacting with adenylate-uridylate rich element-bearing mRNAs. Human skin is the largest organ of the body and acts as a protective barrier against pathogens and injuries. The aim of the present study was to explore the function and potential molecular pathways of AUF1 in human skin cells. AUF1 was overexpressed in human keratinocyte HaCaT cells and human skin fibroblast WS1 cells using adenoviruses and silenced using lentiviruses. AUF1 overexpression facilitated cell proliferation, whereas AUF1 knockdown induced the opposite effect. AUF1 reduced apoptosis but did not affect cell cycle progression. Forced AUF1 expression promoted the migration of human skin cells, as demonstrated by a scratch wound healing assay. Cell senescence was alleviated in AUF1-overexpressing skin cells, while AUF1 knockdown increased cell senescence. WS1 cells with AUF1 overexpression and silencing were used for RNA-sequencing and Kyoto Encyclopedia of Genes and Genomes-based pathway analysis to identify AUF1-affected mRNAs. A total of 18 mRNAs (eight mRNAs with positive associations and 10 mRNAs with negative associations) revealed consistent associations with both AUF1 overexpression and silencing. Enriched pathways associated with AUF1 expression included 'MAPK', 'cell adhesion molecules', 'proteasome', 'cellular senescence' and 'TGF-ß signaling', indicating a complex regulatory network. Overall, the results of the present study revealed that AUF1 is involved in the proliferation, migration and senescence of skin cells in vitro and may be a potential target for cosmetic and disease treatment of skin.

Integrative multi-omic analysis of radiation-induced skin injury reveals the alteration of fatty acid metabolism in early response of ionizing radiation.

BACKGROUND: Radiation-induced skin injury is a serious concern during radiotherapy and accidental exposure to radiation. OBJECTIVE: This study aims to investigate the molecular events in early response to ionizing radiation of skin tissues and underlying mechanism. METHODS: Mice and rats were irradiated with an electron beam. Skin tissues were used for liquid chromatography-mass spectrometry (LC-MS)-based metabolomics, mRNA-Seq and single-cell RNA sequencing (scRNA-Seq). Human keratinocytes (HaCaT) and skin fibroblasts (WS1) were used for functional studies. RESULTS: The integrated analysis of metabolomics and transcriptomics showed that 6 key fatty acid-associated metabolites, 9 key fatty acid-associated genes and multiple fatty acid-associated pathways were most obviously enriched and increased in the irradiated skins. Among them, acyl-CoA dehydrogenase very long chain (ACADVL) was investigated in greater detail due to its most obvious expression difference and significance in fatty acid metabolism. ScRNA-Seq of rat skin from irradiated individuals revealed that ACADVL was expressed in all subpopulations of skin tissues, with variations at different timepoints after radiation. Immunohistochemistry confirmed an increased ACADVL expression in the epidermis from human sample and various animal models, including monkeys, rats and mice. The knockdown of ACADVL increased the radiosensitivity of human keratinocytes and human skin fibroblasts. Silencing of ACADVL facilitated the expression of apoptosis and pyroptosis-related proteins following ionizing radiation. CONCLUSION: This study illustrated that cutaneous fatty acid metabolism was altered in the early response of ionizing radiation, and fatty acid metabolism-associated ACADVL is involved in radiation-induced cell death.